Zhao Xu, Shen Lei, Zheng Jianming, Zhu Haiyan, Li Li, Shi Hong, Chen Zhongqing, Li Qian
Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China.
Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China.
Open Forum Infect Dis. 2023 Mar 21;10(4):ofad151. doi: 10.1093/ofid/ofad151. eCollection 2023 Apr.
To define the role of C1qa in host defense against lung infection, we investigated its susceptibility to cryptococcal lung infection in mice deficient in complement factor C1qa ( ).
We established a wild-type (WT) and C1qa-deficient murine inhalation model with . We compared the host survival rate, inflammatory responses, and pathogenicity of during the infection course between WT and mice.
The mortality rate of C1qa-deficient mice was significantly higher than that of wild-type mice. The increased formation of Titan cells in the lungs was associated with augmented inflammation in C1qa-deficient mice. The capacity of lung homogenate supernatant from C1qa-deficient mice to induce Titan formation in vitro was greater compared with that of wild-type mice. The isolated from the lungs of infected C1qa-deficient mice was more resistant to macrophage killing in vitro and caused significantly higher mortality after administration to mice compared with that isolated from WT mice.
These findings reveal a novel role of C1qa in host defense against infection by regulating host inflammation and pathogen virulence and provide new insight into the C1q-mediated lung environment underlying the transition from yeast to Titan cell.
为了确定补体C1qa在宿主抵抗肺部感染中的作用，我们研究了补体因子C1qa缺陷小鼠对新型隐球菌肺部感染的易感性。
我们建立了野生型（WT）和C1qa缺陷型小鼠吸入新型隐球菌的模型。我们比较了WT小鼠和C1qa缺陷型小鼠在感染过程中的宿主存活率、炎症反应及新型隐球菌的致病性。
C1qa缺陷型小鼠的死亡率显著高于野生型小鼠。C1qa缺陷型小鼠肺中泰坦细胞形成增加与炎症增强有关。与野生型小鼠相比，C1qa缺陷型小鼠肺匀浆上清液在体外诱导泰坦细胞形成的能力更强。从感染的C1qa缺陷型小鼠肺中分离出的新型隐球菌在体外对巨噬细胞杀伤的抵抗力更强，与从WT小鼠分离出的新型隐球菌相比，将其接种给小鼠后导致的死亡率显著更高。
这些发现揭示了C1qa在宿主抵抗新型隐球菌感染中的新作用，即通过调节宿主炎症和病原体毒力发挥作用，并为C1q介导的从酵母细胞向泰坦细胞转变的肺部环境提供了新见解。
